We have cloned several members of the Class II a-mannosidases including two glycoprotein processing enzymes, termed a-mannosidases II and IIx, and two a-mannosidases involved in glycoprotein catabolism. We are presently characterizing the roles of the processing a-mannosidases in the maturation of mammalian glycoproteins by generating mouse knockouts for the processing mannosidases in collaboration with Drs. Jamie Marth and Michiko Fukuda. In addition, these a-mannosidase II knockout mice will also act as animal models for the human genetic disease characterized by an enzymatic defect in a-mannosidase II (HEMPAS disease).